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Biocompatability in the Characterisation of Medical Devices

Biocompatibility can be defined as the properties of materials being compatible with the body by not demonstrating potentially harmful local or systemic responses upon contact and subsequent evaluation. Biocompatible materials should not produce adverse effects when exposed to the body or bodily fluids.

For almost all medical devices that have more than transient contact with human tissue, biocompatibility evaluation is required by regulatory bodies to confirm the safety of the device or material. Evaluation of the biocompatibility of a medical device is one part of the overall safety assessment of a device and is intended to determine the potential toxicity resulting from bodily contact.  Biocompatibility assessment can be achieved through the combination of testing, safety evaluations as well as information derived from material and chemical characterization.

Biocompatibility data can be obtained by conducting testing according to guidance documents developed by the International Organization for Standardization (ISO) as well as geography-specific guidance documents.  For ISO requirements, the biocompatibility testing approach and requirements are contained in the ISO 10993 series of guidance documents. ISO-10993-1 is a critical component of the medical device risk assessment process and a key document for understanding the overall requirements and selection of tests. ISO 10993-2 covers animal welfare requirements and supports the 3 R’s (reduction, replacement, and refinement) for testing, while the rest of the series, including Part 18-chemical characterization of the device, cover specific procedures and provides details related to the testing designs.

Over the past decade, the medical device industry has seen a legitimately comprehensive overhaul in the biological evaluation process of medical devices.  The recent updates to ISO 10993-1(2018), and 10993-18(2020) highlight the significant changes in approach that have occurred over time while also providing a more detailed outline of expectations.   The biological evaluation process is no longer a check-boxing exercise of conducting toxicology testing per the ISO 10993-1 matrix. Instead ISO-10993-1 should be thought of as the framework that can be used to design a biocompatibility testing program for your individual device.

Biocompatibility evaluations must be based on a sound scientific rationale and be strategic in design.  A thorough understanding of the device materials including chemistry is expected and the biological strategy should be the result of a close partnership between the Chemist and Toxicologist with an integration of the chemical and biological data. In fact, a carefully constructed biological evaluation plan (BER) tailored to a specific device and its available dataset, can actually minimize the amount of required biocompatibility testing especially when there is a comprehensive understanding of the device materials and processing.

As a regulatory-defendable and integrated scientific strategy that is well documented in a biologic evaluation plan (BEP) is required, an experienced Toxicologist should be engaged to develop the approach.   This expert may be someone internal to the company, especially in larger organizations, or outsourced to an experienced consulting Toxicologist for manufacturers/developers that do not have this internal capability.

The biocompatibility evaluation plan of a device considers many factors, including: (i) the chemical and physical nature of its component materials and the device itself (ii) the nature of the contact with the body (ii)  the duration of the exposure and (iv)  the intended use and patient population.

The biocompatibility of devices is investigated using analytical chemistry, safety assessments and in vitro and in vivo testing.  It is important to note that this evaluation can be considered a risk assessment of all data pertinent to the safety of the device.

The chemical characterization evaluation provides the critical information needed to conduct a detailed toxicological risk assessment and may help establish that a device has a low potential of producing a particular biological effect which can minimize the biocompatibility testing captured in the evaluation plan  Additionally, information on a predicate device or on the components themselves may also impact the risk profile and testing requirements.

Considering the potential risks identified as well as their impact, a plan should be developed that appropriately address the risks. The plan should minimize unnecessary testing while maintaining compliance with relevant standards in order to support the safe use of the product.  The plan should also be considered a living document so as new information is obtained, the plan would be updated accordingly.

The identified testing should be performed on the sterile final product, or representative samples from the final product or materials processed in the same manner as the final product including the sterilization method. As a rule, the biocompatibility toxicity testing should be performed in compliance with Good Laboratory Practice (GLP) regulations.

Once the testing is completed, the overall assessment of the biological data along with the key material and chemical assessments should be documented in a biological evaluation report (BER) intended to support a regulatory submission and protect patient safety.

In summary, the regulatory requirements, and expectations for biocompatibility assessment for medical devices have evolved rapidly over the last decade and provide an opportunity for a device specific approach.  Biocompatibility evaluations must be strategic and based on a sound scientific rationale including an in-depth understanding of the manufacturing and chemistry.